Pharmacological basis for the neurocognitive effect of atypical antipsychotic drugs

Toshihide Kuroki, Tatsuo Nakahara

Research output: Contribution to journalReview articlepeer-review


Cognitive impairment is a key feature of schizophrenia and may be the most important determinant of outcome in schizophrenia. Certain kinds of atypical antipsychotic drugs (APDs) have been reported to improve cognitive symptoms of schizophrenia, although little is known about the mechanism of this action. The aim of this paper is to consider the pharmacological basis for the superior efficacy of atypical APDs on cognitive function. In animal studies, atypical APDs have demonstrated to modulate dopamine (DA) and acetylcholine (Ach) neurotransmission preferentially in the cortical areas. Atypical APDs, unlike typical APDs, increase DA release in the prefrontal cortex to a greater extent than in the subcortical regions such as the striatum and nucleus accumbens, as measured by in vivo microdialysis. This preferential effect of atypical APDs may be related to their common receptor binding profiles such as greater affinities to serotonin (5-HT)2A receptors than DA-D2 receptors, in addition with significant ability to stimulate 5-HT1A receptors. Atypical APDs, but not typical APDs, also induce Ach release in the prefrontal cortex and hippocampus. Despite antagonism by some atypical APDs to muscarinic Ach receptors, these drugs may counteract it with an increase in Ach release. Thus, the greater ability of atypical APDs than typical APDs to enhance the release of DA and Ach in the cortical regions may be related to the neurocognitive effect of atypical APDs that are thought to ameliorate the hypofrontality responsible for cognitive deficits of schizophrenia. Copyright

Original languageEnglish
Pages (from-to)10-20
Number of pages11
JournalClinical Psychopharmacology and Neuroscience
Issue number1
Publication statusPublished - Apr 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Behavioral Neuroscience
  • Pharmacology (medical)


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